Bruno Silva Andrade1, Preetam Ghosh2, Debmalya Barh3, Sandeep Tiwari4, Raner José Santana Silva5, Wagner Rodrigues de Assis Soares6, Tarcisio Silva Melo1, Andria Santos Freitas5, Patrícia González-Grande5, Lucas Sousa Palmeira1, Luiz Carlos Junior Alcantara4,7, Marta Giovanetti4,7, Aristóteles Góes-Neto8, Vasco Ariston de Carvalho Azevedo4. 1. Laboratório de Bioinformática e Química Computacional, Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia (UESB), Jequié, Bahia, 45205-490, Brazil. 2. Department of Computer Science, Virginia Commonwealth University, Richmond, VA, 23284, USA. 3. Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Purba Medinipur, India. 4. Laboratório de Genética Celular e Molecular, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, MG, Brazil. 5. Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, BA, Brazil. 6. Departamento de Saúde II, Universidade Estadual do Sudoeste da Bahia., Jequié, BA, Brazil. 7. Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. 8. Laboratório de Biologia Molecular e Computacional de Fungos, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
Abstract
Background: SARS-CoV-2 is the causal agent of the current coronavirus disease 2019 (COVID-19) pandemic. They are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity. The approximately 33.8 kDa M pro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that M pro could be a potential drug target for Coronaviruses. Methods: Herein, we performed computational ligand screening of four pharmacophores (OEW, remdesivir, hydroxychloroquine and N3) that are presumed to have positive effects against SARS-CoV-2 M pro protease (6LU7), and also screened 50,000 natural compounds from the ZINC Database dataset against this protease target. Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 11 best selected ligands, namely ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as beta-carboline, alkaloids, and polyflavonoids, and all displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as other known ligands. Conclusions: Our results suggest that these 11 molecules could be effective against SARS-CoV-2 protease and may be subsequently tested in vitro and in vivo to develop novel drugs against this virus. Copyright:
Background: SARS-CoV-2 is the causal agent of the current coronavirus disease 2019 (COVID-19) pandemic. They are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity. The approximately 33.8 kDa M pro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that M pro could be a potential drug target for Coronaviruses. Methods: Herein, we performed computational ligand screening of four pharmacophores (OEW, remdesivir, hydroxychloroquine and N3) that are presumed to have positive effects against SARS-CoV-2 M pro protease (6LU7), and also screened 50,000 natural compounds from the ZINC Database dataset against this protease target. Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 11 best selected ligands, namely ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as beta-carboline, alkaloids, and polyflavonoids, and all displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as other known ligands. Conclusions: Our results suggest that these 11 molecules could be effective against SARS-CoV-2 protease and may be subsequently tested in vitro and in vivo to develop novel drugs against this virus. Copyright:
Authors: Marisa G Santibáñez-Morán; Edgar López-López; Fernando D Prieto-Martínez; Norberto Sánchez-Cruz; José L Medina-Franco Journal: RSC Adv Date: 2020-07-01 Impact factor: 4.036